Combined analysis of lncRNA and mRNA emphasizes the potential role of tryptophan-mediated regulation of muscle development in weaned piglets by lncRNA.

Pork is an important high-value protein source that fulfills the nutritional requirements for normal growth development, repair, and metabolism. Tryptophan (Trp), a crucial amino acid for piglet growth performance and muscle development, has an essential yet unclear regulatory mechanism. To investigate the biological basis of Trp regulation of piglet muscle development and identify the related regulatory pathways, we studied 20 weaned piglets. The piglets were divided into control (CON, 0.14% Trp) and high Trp (HT, 0.35% Trp) groups. They were fed with different Trp concentrations for 28 d, after which we collected the longissimus dorsi (LD) muscle for histomorphometric analysis and RNA extraction. Our results showed that the HT diet significantly increased the average daily weight gain, myocyte number, and muscle fiber density in weaned piglets. We then analyzed the differentially expressed (DE) genes in the LD muscle through RNA sequencing (RNA-seq). We identified 253 lncRNAs and 1,055 mRNAs mainly involved in myoblast proliferation and myofiber formation, particularly through the FoxO and AMPK signaling pathways and metabolism. Further analysis of the DE lncRNA targeting relationship and construction of a protein-protein interaction network resulted in the discovery of a novel lncRNA, XLOC_021675, or FRPMD, and elucidated its role in regulating piglet muscle development. Finally, we confirmed the RNA-seq results by reverse transcription polymerase chain reaction (RT-PCR). This study provides valuable insights into the regulatory mechanism of lncRNA-mediated Trp regulation of muscle development in weaned piglets offering a theoretical basis for optimizing piglet dietary ratios and enhancing pork production.

Tryptophan (Trp) is one of the key amino acids for pig growth and muscle development. We have verified the crucial role of Trp in enhancing daily weight gain and promoting muscle development in weaned piglets. We also identified the significant influence of long noncoding RNA (lncRNA) as regulators of piglet muscle development through transcriptome analysis of the longissimus dorsi (LD) muscle of weaned piglets. Functional analysis of differentially expressed (DE) lncRNAs and mRNAs in the LD muscle of piglets yielded a functional enrichment network of mRNAs co-expressed and co-localized with DE lncRNAs. To gain insights into the regulatory mechanisms of DE lncRNAs in transcription and translation, we established targeting relationships and protein­protein interaction (PPI) networks for DE lncRNAs. We identified a novel lncRNA (XLOC_021675) with a significant role in piglet muscle development named FRPMD. This study is a valuable reference for optimizing piglet diets and provides a solid foundation for further research on piglet muscle development.

Circular RNAs mediate the regulation of maternal placental nutrient transport and fetal development by sugar-sweetened beverages.

Epidemiological and experimental studies have demonstrated a strong association between maternal diet and fetal birth weight, obesity, and metabolic syndrome. We investigated the pathways and modes of action of circular RNAs (circRNAs) that mediate the regulation of maternal reproductive performance and fetal development by sugar-sweetened beverages (20 % sucrose water, SSBs) using C57BL/6J mice as a model. Results showed that SSBs significantly increased the reproductive performance (P<0.05), body weight (P<0.01), fetal birth weight (P<0.05), placental weight (P<0.01), and the expression of nutrient transporter genes in the placenta and fetal liver (P<0.05), mainly by accelerating the maternal energy metabolism during pregnancy. However, maternal serum biochemical indices, antioxidant indices, and pathological damage to the liver and placenta predicted that the mother would be at greater health risks during this period. Moreover, transcriptomics results indicated that the differentially expressed (DE) circRNAs in the placenta regulate the maternal multiple metabolic pathways and the placental nutrient transport efficiency by sponging miRNAs and forming growth factors and proteins, ultimately improving the maternal reproductive performance. In addition, we verified the reliability of the sequencing results using reverse transcription polymerase chain reaction and identified the possibility of DE circRNAs binding to nutrient transporter genes using targeting relationship prediction. Finally, we constructed a correlation network that regulates maternal placental nutrient transport based on DE circRNAs, targeted miRNAs and nutrient transport-related genes. This study will provide scientific dietary guidance for pregnant women and new research ideas for preventing and treating pregnancy complications.

Circular RNAs Mediate the Effects of Dietary Tryptophan on the Transformation of Muscle Fiber Types in Weaned Piglets.

The nutritional composition of the diet significantly impacts the overall growth and development of weaned piglets. The current study aimed to explore the effects and underlying mechanisms of dietary tryptophan consumption on muscle fiber type transformation during the weaning period. Thirty weaned piglets with an average body weight of 6.12 ± 0.16 kg were randomly divided into control (CON, 0.14% Trp diet) and high Trp (HT, 0.35% Trp) groups and maintained on the respective diet for 28 days. The HT group of weaned piglets exhibited highly significant improvements in growth performance and an increased proportion of fast muscle fibers. Transcriptome sequencing revealed the potential contribution of differentially expressed circular RNAs toward the transformation of myofiber types in piglets and toward the regulation of expression of related genes by targeting the microRNAs, miR-34c and miR-182, to further regulate myofiber transformation. In addition, 145 DE circRNAs were identified as potentially protein-encoding, with the encoded proteins associated with a myofiber type transformation. In conclusion, the current study greatly advances and refines our current understanding of the regulatory networks associated with piglet muscle development and myofiber type transformation and also contributes to the optimization of piglet diet formulation.

Factors influencing civil servants' willingness to implement cardiopulmonary resuscitation in Chongqing, China: Based on the theory of planned behavior.

Background: Timely bystander cardiopulmonary resuscitation is the key to improving the survival rate of out-of-hospital cardiac arrest. Civil servants are potential bystander CPR providers. This study aimed to explore civil servants' willingness to implement CPR in Chongqing, identify the influencing factors and mechanisms affecting civil servants' willingness to perform CPR, and then seek countermeasures to improve civil servants' willingness to implement CPR. Methods: We introduced the theory of perceived risk into the theory of planned behavior, developed a 7-point Likert scale based on the extended theory of planned behavior, and conducted a questionnaire survey on civil servants in Chongqing, China. Descriptive statistical analysis and one-way ANOVA were employed to explore respondents' willingness and differences. Structural equation modeling was used to analyze the relationship between attitude, subjective norm, perceived behavioral control and perceived risk and respondents' willingness to implement CPR. Results: A total of 1235 valid questionnaires were included for analysis. 50.1 % of respondents were willing to implement CPR. Male, over 40 years old, living with the elderly, having previous experience performing CPR on another person, and having higher CPR knowledge scores were associated with a more positive willingness to perform CPR. Attitude, subjective norm and perceived behavioral control had significant positive effects on willingness, and the standardized regression coefficients were 0.164, 0.326 and 0.313, respectively. The perceived risk has a significant negative effect on willingness, and the standardized regression coefficient was -0.109. The four latent variables accounted for 44.2 % of the variance in the willingness of civil servants to implement CPR. Conclusions: The willingness of civil servants in Chongqing to implement CPR needs to be improved, and the countermeasures to enhance the subjective norm and perceived behavioral control of civil servants should be emphasized, such as developing a social support network for rescuing conduct, establishing regular training mechanisms and improving the practical applicability and popularization of the Chinese-style "Good Samaritan Law" etc., to improve the willingness of civil servants in Chongqing to implement CPR.

Pre-Drying of Chlorine-Organic-Contaminated Soil in a Rotary Dryer for Energy Efficient Thermal Remediation.

In response to the current problem of the high energy consumption of direct thermal desorption systems when treating soils with a high moisture content, we propose using the waste heat of the system to pre-dry soil to reduce its moisture. Taking chlorine-organic-contaminated soil as an object, an experimental study on the drying and pollutant desorption characteristics of soil in an indirect rotary dryer was carried out. The results show that the non-isothermal drying process was divided into warm-up and falling rate periods, and no constant period was observed. The higher the rotation speed, the lower the soil outlet temperature and the higher the drying tail gas temperature. Soil outlet and dry tail gas temperatures were lower for soils with a higher moisture content. Benzene and cis-1,2-dichloroethylene are easily desorbed. Therefore, the disposal of dry tail gas should be determined according to the type and concentration of soil pollutants present. The volumetric heat transfer coefficient was found to be 85-100 W m-3 °C-1, which provides a key parameter for the size design of a rotary dryer.

Knowledge, training and willingness to perform bystander cardiopulmonary resuscitation among university students in Chongqing, China: a cross-sectional study.

OBJECTIVE: To evaluate knowledge of cardiopulmonary resuscitation (CPR) among Chinese college students and their attitude towards participating in CPR training and willingness to perform bystander CPR. DESIGN: A cross-sectional study. PARTICIPANTS: A total of 1128 college students were selected through a multistage stratified random sampling method from 12 universities in Chongqing, China. PRIMARY AND SECONDARY OUTCOMES: Primary outcomes included CPR knowledge and willingness to participate in training and perform bystander CPR; secondary outcomes included CPR training experience and obstacles to training and performing CPR. RESULTS: The average score on CPR knowledge was 2.078 (±1.342). Only 45.5% of the respondents were willing to participate in CPR training. Women, respondents who were postgraduate or above, with liberal arts as major and with high CPR knowledge level were more willing to participate in CPR training. A total of 47.2% of the respondents were willing to provide simple assistance, such as checking the consciousness and breathing of the patient and dialling 120 (medical emergency call). Only 34.1% indicated their willingness to perform bystander CPR on strangers. Perceived behavioural control, behavioural attitudes and subjective norms are positive predictors of willingness to provide bystander CPR. CONCLUSIONS: CPR knowledge and training rate were low among Chongqing college students. Willingness to participate in training and perform bystander CPR was also low. Improving legislation, strengthening training programmes, incorporating CPR training into the school curriculum and reshaping the social and public culture of offering timely help to those in need are recommended strategies to improve bystander CPR performance.

All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide.

Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic. Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy. Therefore, all-stage precisional glioma targeted therapy regimens that could efficiently deliver drugs to glioma cells and GSCs after overcoming multiple barriers have received increasing scrutiny. Methods: A polymeric micelle-based drug delivery system was developed by modifying a "Y-shaped" well-designed ligand of both GRP78 protein and quorum sensing receptor to achieve all-stage precisional glioma targeting, then we evaluated the targeting ability and barrier penetration ability both in vitro and in vivo. In order to achieve all-stage precisional therapy, we need kill both GSCs and glioma related cells. Parthenolide (PTL) has been investigated for its selective toxicity to glioma stem cells while Paclitaxel (PTX) and Temozolomide (TMZ) are widely used in experimental and clinical therapy of glioma respectively. So the in vivo anti-glioma effect of combination therapy was evaluated by Kaplan-Meier survival analysis and immunohistochemical (IHC) examination of tumor tissues. Results: The "Y-shaped" well-designed peptide, termed DWVAP, exhibited excellent glioma (and GSCs) homing and barrier penetration ability. When modified on micelle surface, DWVAP peptide significantly enhanced accumulation of micelles in brain and glioma. In addition, DWVAP micelles showed no immunogenicity and cytotoxicity, which could guarantee their safety when used in vivo. Treatment of glioma-bearing mice with PTL loaded DWVAP modified PEG-PLA micelles plus PTX loaded DWVAP modified PEG-PLA micelles or PTL loaded DWVAP modified PEG-PLA micelles plus TMZ showed improved anti-tumor efficacy in comparison to PTL and PTX loaded unmodified micelles or PTL loaded unmodified micelles plus TMZ. Conclusion: Combination of all-stage targeting strategy and concomitant use of chemotherapeutics and stem cell inhibitors could achieve precise targeted therapy for glioma.

EGFR/EGFRvIII Dual-Targeting Peptide-Mediated Drug Delivery for Enhanced Glioma Therapy.

Tumor-homing peptides have been widely used to mediate active targeted drug delivery. l-AE is a reported targeting peptide demonstrating high binding affinity to epidermal growth factor receptor (EGFR) and mutation variant III (EGFRvIII) overexpressed on neovasculature, vasculogenic mimicry, tumor cells, and tumor stem cells. To improve its proteolytic stability, a d-peptide ligand (termed d-AE, the enantiomer of l-AE) was developed. d-AE was confirmed to bind receptors EGFR and EGFRvIII with targeting capability comparable to l-AE. In vivo biodistribution demonstrated the superiority of d-AE in prolonged circulation and enhanced intratumoral accumulation. Furthermore, stabilized peptide modification endowed micelles higher transcytosis efficiency and penetrating capability on blood-brain tumor barrier/U87 tumor spheroids coculture model. When paclitaxel (PTX) was loaded, d-AE-micelle/PTX demonstrated excellent antitumor effect in comparison to Taxol, micelle/PTX, and l-AE-micelle/PTX. These findings indicated that the multitargeted drug delivery system enabled by d-AE ligand provides a promising way for glioma therapy.

GRP78 enabled micelle-based glioma targeted drug delivery.

GRP78, a specific cancer cell-surface marker, is implicated in cancer cells proliferation, apoptosis resistance, metastasis and drug resistance. l-VAP (SNTRVAP) is a tumor homing peptide exhibiting high binding affinity in vitro to GRP78 protein overexpressed on glioma, glioma stem cells, vasculogenic mimicry and neovasculature. Even though short peptides are often non-immunogenic and demonstrate high affinity to tumor cells, their targeting efficacy is always undermined by rapid blood clearance and enzymatic degradation. In the present study, two d peptides RI-VAP (retro inverso isomer of l-VAP) and d-VAP (retro isomer of l-VAP) were developed by structure-guided peptide design and retro-inverso isomerization technique for glioma targeting. RI-VAP and d-VAP were predicted to bind their receptor GRP78 protein with similar binding affinity, which was experimentally confirmed. The results of in vivo imaging demonstrated that RI-VAP and d-VAP had remarkably advantage over l-VAP for tumor accumulation. In addition, RI-VAP and d-VAP modified paclitaxel-loaded polymeric micelle had better anti-tumor efficacy in comparison to taxol, paclitaxel-loaded plain micelles and l-VAP modified micelles. Overall, the VAP modified micelles suggested in the present study could effectively achieve glioma-targeted drug delivery, validating the potential of the stable VAP peptides in improving the therapeutic efficacy of paclitaxel for glioma.

d-Retroenantiomer of Quorum-Sensing Peptide-Modified Polymeric Micelles for Brain Tumor-Targeted Drug Delivery.

Compared to that of other tumors, various barriers, such as the blood-brain barrier (BBB), enzymatic barriers, and the blood-brain tumor barrier, severely impede the successful treatment of gliomas. Peptide ligands were frequently used as targeting moieties to mediate brain tumor-targeted drug delivery. LWSW (SYPGWSW) is a recently reported quorum-sensing (QS) peptide that is able to efficiently cross the BBB. Even though linear LWSW traverses the BBB in vitro, its in vivo targeting ability has been greatly impaired due to proteolysis. Here, we developed a stable peptide, DWSW (DWDSDWDGDPDYDS), using the retro-inverso isomerization technique to achieve an enhanced antiglioma effect. In vitro studies have demonstrated that both the LWSW and DWSW peptides possessed excellent tumor-homing properties and barrier-penetration abilities, whereas DWSW exhibited exceptional stability in serum and maintained its targeting ability after serum preincubation. In vivo, DWSW-modified probes and micelles accumulated more efficiently in the glioma region in comparison with LWSW-modified probes and micelles because of full resistance to proteolysis in blood circulation. As expected, DWSW-modified paclitaxel (PTX)-loaded micelles (DWSW Micelle/PTX) exhibited the longest median survival time among glioma-bearing nude mice. Our results suggested that the QS peptide appears to be a promising targeting moiety, with potential applications in glioma-targeted drug delivery.